Novel selective inhibitors of aminopeptidases that generate antigenic peptides
2013
Papakyriakou, Athanasios | Zervoudi, Efthalia | Theodorakis, Emmanuel A. | Saveanu, Loredana | Stratikos, Efstratios | Vourloumis, Dionisios
Endoplasmic reticulum aminopeptidases, ERAP1 and ERAP2, as well as Insulin regulated aminopeptidase (IRAP) play key roles in antigen processing, and have recently emerged as biologically important targets for manipulation of antigen presentation. Taking advantage of the available structural and substrate-selectivity data for these enzymes, we have rationally designed a new series of inhibitors that display low micromolar activity. The selectivity profile for these three highly homologous aminopeptidases provides a promising avenue for modulating intracellular antigen processing.
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